AMPARs and NMDAR Diversity Flashcards
Which is faster, NMDARs or AMPARs?
AMPARs, by a lot
What is a property of all AMPARs (that is not subunit dependent)?
High Open probability and rapid activation
What is a property of AMPARs that IS Subunit dependent?
Desensitization recovery (how long it takes before a stimulus depolarizes the channel, different cases for sound or light)
Describe the shared architecture of AMPARs and NMDARs in terms of their domains, polymerity, and shape
Amino Terminal Domain
Ligand Binding Domain
TransMembrane Domain
Homo or heterotetramers with different subgroups that alter pharmacology (two sets of 2 subunits)
Crossing over of 2 proteins between ATD and LBD
What is unique about the GluA2 AMPA Receptor subunit?
They are edited at the Q/R/N site of the M2 loop
Where is the Q/R/N site located in the assembled protein and what is the function?
At the apex of the pore, allows the pore to open/close by twisting open (on a matter of angstroms)
What did Prof Bowie notice about when depolarizing a cell?
Ohm’s law (P = IR) did not apply
meaning something must be offsetting the rectification
What is a property of polyamines?
They can restore rectification
What is the only AMPAR subunit that does not have rectification?
GluA2
How do polyamines block AMPARs?
The Q/R/N site creates a block site that is electronegative, big clunky polyamine hesitates inside and gets stuck
AMPARs preferentially form what type of polymer? What form is favored and which are unstable?
Heteromers
Some homomers are permitted but mostly 2:2 stoichiometry is favored
What are the auxiliary subunits mentioned in class and what do they do?
TARP, Cornichons, CKAMP44, SynDIG1, GSG1L
They bind to AMPA receptors and modify functions
What is an advantage of the heavy regulation of AMPARs?
Different regions of the brain have specific regulation, allowing for drug specificity
What is the role of TARP?
Bus that transports AMPARs to the synapse
How do TARPs and CNIHs regular AMPAR gating behaviour?
Increasing the signalling time through the KGK site of GluA2